Gestational weight gain adequacy among twin pregnancies in France

Abstract The objective of this paper is to describe gestational weight gain (GWG), to assess the applicability of the 2009 Institute of Medicine (IOM) guidelines, and to derive a GWG adequacy classification within a French cohort. We included twins from the national, prospective, population‐based JUmeaux MODe d'Accouchement (JUMODA) cohort study (2014–2015). Following the IOM approach, we selected a ‘standard’ population of term pregnancies with ‘optimal’ birthweight (≥2500 g; n = 2562). GWG adequacy (insufficient; adequate; excessive) was defined using IOM recommendations (normal body mass index [BMI]: 16.8–24.5 kg [also utilized for underweight BMI]; overweight: 14.1–22.7 kg; obese: 11.4–19.1 kg). Additionally, using the IOM approach, we determined the 25th and 75th percentiles of GWG in our standard population to create a JUMODA‐derived GWG adequacy classification. GWG and GWG adequacy were described, overall and by BMI and parity. In the JUMODA standard population of term twin livebirths with optimal birthweight, mean GWG was 16.1 kg (standard deviation 6.3). Using IOM recommendations, almost half (46.5%) of the women had insufficient and few (10.0%) had excessive GWG, with similar results regardless of BMI or parity. The 25th and 75th percentiles of GWG in the JUMODA standard population (underweight: 13–21 kg; normal weight: 13–20 kg; overweight: 11–19 kg; obese: 7–16 kg) were lower than the IOM recommendations. The IOM recommendations classified a relatively high percentage of French women as having insufficient and a low percentage as having excessive GWG. Additional research to evaluate recommendations in relation to adverse perinatal outcomes is needed to determine whether the IOM recommendations or the JUMODA‐derived classification is more appropriate for French twin gestations.


| INTRODUCTION
In 2009, the United States Institute of Medicine (IOM) released updated guidelines for gestational weight gain (GWG), with specific guidelines added for twin pregnancies (Rasmussen & Yaktine, 2009).
Nonetheless, the IOM acknowledged that the guidelines for GWG in twin pregnancies were provisional because the committee was not able to evaluate the causal association between GWG and adverse outcomes and the trade-offs between maternal and child outcomes, as was done for the singleton GWG recommendations.
Instead, the IOM recommendations for twin pregnancies were based on the 25th and 75th percentiles of GWG in a historical USA cohort  of term (37-42 weeks GA) livebirths with optimal birthweight (mean twin birthweight of ≥2500 g [Luke et al., 2003]) and due to small sample size, recommendations for underweight women were not provided (Rasmussen & Yaktine, 2009).
Given the IOM recommendations were not intended for use outside the USA (particularly outside developed countries, in populations with shorter or thinner women, or where adequate obstetric services are unavailable [Rasmussen & Yaktine, 2009]), verification of their applicability in specific obstetric populations and estimation of potential cohort-derived percentiles is important to ensure pregnant women receive appropriate GWG counselling.

| Study population
Of 8823 women recruited immediately following delivery into the initial JUMODA cohort (Supporting Information: Figure 1), we excluded women not delivering two liveborn twins (n = 320), as pregnancies with one or more stillbirth may have distinct GWG patterns, or with missing (n = 1303) or implausible GWG (>50 kg; n = 3). Then, we excluded women with preterm birth (before 37 weeks GA; n = 3732), missing BMI (n = 66; GWG adequacy determination not possible), or with mean twin birthweight <2500 g (n = 4109) to create a standard population of twin pregnancies

Key messages
• Using the 2009 Institute of Medicine (IOM) recommendations to define gestational weight gain (GWG) adequacy in our French cohort classified almost half of women as having insufficient GWG and a relatively low percentage as having excessive GWG.
• The USA-derived IOM definition for adequate GWG may not apply in France or in other non-USA, contemporary obstetric populations.
• Additional research in large, population-based contemporary cohorts with prospective GWG ascertainment and assessment of GWG adequacy classifications in relation to adverse outcomes is needed to inform evidence-based GWG recommendations for twin pregnancies.
(n = 2562) equivalent to that utilized to derive the IOM guidelines (term livebirths with optimal birthweight). Data utilized were collected by trained research nurses through chart abstraction.

| Statistical analysis
Maternal characteristics and GWG of the JUMODA standard population were described. GWG was described overall and by GA at delivery (means, standard deviations [SDs], 25th and 75th percentiles), with further stratification by BMI.
GWG adequacy based on the IOM recommendations was determined in the JUMODA standard population to assess their applicability in a French cohort similar to that in which they were derived (in terms of GA at delivery and twin birthweight). Then, we created a JUMODA-cohort derived GWG adequacy classification by utilizing the approach the IOM used to generate their recommendations: we determined the 25th and 75th percentiles of total GWG, by prepregnancy BMI, within our standard population (women delivering twin livebirths at 37-42 weeks GA with optimal birthweight [≥2500 g]). GWG adequacy based on the JUMODA-derived classification, overall and by prepregnancy BMI and parity, was determined in the standard population to verify the performance of the classification. Additionally, in line with the IOM report, adjusted cumulative GWG was presented as least square means (standard error) from multivariable linear regression models adjusted for smoking in pregnancy, parity, chorionicity, Pre-eclampsia, diabetes or gestational diabetes, and GA at delivery (days).
We used SAS software version 9.4 for Windows (SAS Institute Inc.) for statistical analyses.

| Ethical statement
Women received information and provided oral informed consent for study participation before recruitment and data collection. JUMODA was approved by the National Data Protection Authority, the

| RESULTS
In the JUMODA standard population of term twin livebirths with optimal birthweight, most women were normal weight prepregnancy BMI (59.9%), were born in France (75.6%), and did not smoke in pregnancy (90.4%; Table 1). Mean cumulative GWG was 16.1 kg (SD 6.3; 25th, 75th percentiles of total GWG 12, 20 kg) and increased from 37 to ≥39 weeks (Table 2; Figure 1). GWG was inversely related to prepregnancy BMI, but patterns were inconsistent across BMI strata for the association between GWG and GA at delivery. Table 3  In line with our overall results, previous cohort studies with serial measures of GWG in twin gestations have shown increasing GWG curves over pregnancy (Hutcheon et al., 2018;Luke et al., 2003). The differences by prepregnancy BMI in the association between GWG and GA in our stratified analysis are intriguing and may point to the delicate physiologic balance between promotion of foetal growth (a component of GWG) versus maturity (Blickstein, 2002) and the need to meet nutritional demands while avoiding adverse effects of excess GWG, particularly given the inverse association found among women with underweight prepregnancy BMI who gain the most weight and may also be less able to sustain its incumbent physical demands. Given our small sample sizes after 39 weeks in this stratified analysis, additional prospective research in larger samples is needed confirm our results and to understand underlying physiology.
GWG was lower in our cohort in comparison to the IOM cohort, though our estimates increased slightly after adjusting for confounders, which may be due to differences both in the United States and French obstetric populations broadly and in the two standard twin cohorts specifically. As noted previously, the French obstetric T A B L E 1 Maternal and pregnancy characteristics in a standard population of liveborn term births (37-42 weeks gestation) with mean birthweight ≥2500 g (JUMODA cohort, 2014(JUMODA cohort, -2015France)  had excessive GWG (Lipworth et al., 2022). However, in examining individual studies, differences in the percentages were noted between North American and non-North American populations.
c Derived from a historical US cohort  of term (37-42 weeks gestational age) twin livebirths with mean twin birthweight of ≥2500 g from four hospitals; separate recommendation for underweight women not provided due to small sample size. d JUMODA standard population of term (37-42 weeks gestational age) twin livebirths with mean twin birthweight ≥2500 g (2014-2015; France). e Values for least square means (SE mean) from models adjusted for diabetes and gestational diabetes, Pre-eclampsia, smoking during pregnancy, primiparity, placental membranes (monochorionicity and missing chorionicity) and length of gestation. f Values for least square means (SE mean) from multivariable linear regression models adjusted for smoking in pregnancy, parity, chorionicity, Pre-eclampsia, diabetes or gestational diabetes and gestational age at delivery (days).
The differences noted between these studies and ours could be due study locations, as the IOM noted that their guidelines were specifically intended for USA populations (Rasmussen & Yaktine, 2009), suggesting the provisional IOM recommendations may indeed be applicable in North American obstetric populations.
Regardless of the differences noted above, studies have consistently found that inadequate GWG based on the IOM recommendations for twin gestations was associated with adverse outcomes. In North American twin cohorts, inadequate GWG based on the IOM recommendations was associated with adverse outcomes, in particular birthweight outcomes (Fox et al., 2011;Gavard & Artal, 2014;Lal & Kominiarek, 2015;Lin et al., 2022;Lipworth et al., 2021;Liu et al., 2021;Lutsiv et al., 2017). Similiarly, except in one Japanese study , inadequate GWG based on IOM recommendations was nonetheless associated with adverse outcomes in non-North American twin cohorts (Algeri et al., 2018;Chen et al., 2018;Choi et al., 2020;Lin et al., 2019;Wang et al., 2018) create the IOM recommendations, potential differences (beyond time period and location) between study populations are difficult to assess and therefore it is unclear whether the differences noted are due to differences in the study populations or the inadequacy of the IOM guidelines. Similarly, while we adjusted for the same covariates to determine adjusted means, it is possible our definitions for these variables were not identical to those used by the IOM, as they were not explicitly defined in their methods.
Finally, given the complexities of incorporating these analyses, we did not include outcome data (to create outcome-based recommendations or to evaluate the performance of the IOM recommendations and JUMODA classification). Therefore, it is unclear whether the IOM recommendations or JUMODA-derived adequacy classification may be more clinically useful. To appropriately assess outcomes, careful consideration of which outcomes to evaluate, appropriate confounders to control for in adjusted analyses (given the variation in mechanisms underlying the association between insufficient/excessive GWG and different outcomes), and the correct study population (a more general population rather than the standard population would be necessary, in particular to evaluate preterm delivery or small for GA/large for GA) would be essential and better addressed in future research.

| CONCLUSION
Using IOM recommendations to define GWG adequacy in our French cohort classified almost half of the women as having insufficient and a relatively low percentage as having excessive GWG. As we did not assess outcomes, it is unclear whether the IOM recommendations or the JUMODA-derived classification is more appropriate for French twin gestations. Additional research in large, population-based contemporary cohorts with prospective GWG assessment and assessment of adverse outcomes is needed to determine evidence-based recommendations for optimal GWG in twin pregnancies.

AUTHOR CONTRIBUTIONS
Thomas Schmitz contributed substantially to the design, data acquisition, and project administration of the JUMODA study. All authors critically reviewed and approved the final manuscript.